Is FLRT1 p.Leu233= (c.699G>A) pathogenic?

FLRT1 p.Leu233= (c.699G>A) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-28). Very rare (popmax 0.0011%, sas); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Leu233= (c.699G>A)?

FLRT1 p.Leu233= (c.699G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Leu233= (c.699G>A) in the general population?

FLRT1 p.Leu233= (c.699G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

FLRT1 p.Leu233=

c.699G>A · rs754088054 · VCV1101046

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

peripheral neuropathy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.5	GERP 0.51, phastCons 1
Overall
CADD	7.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,611,714 alleles · very rare exomes 2/1,459,526 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	0.000254%	393,328

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FLRT1
Protein: p.Leu233=
Coding: c.699G>A
MANE Select: NM_013280
dbSNP: rs754088054
Type: single nucleotide variant
Location: chr11:64116966 (GRCh38)

Full FLRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peripheral neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/flrt1-p-leu233 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown